Pruritus is a condition that involves localized or general itching, which often leads to the urge to scratch and the stimulation of sensory nerve endings. Scratching can be severe, resulting in irritation and inflammation of the skin, as well as bleeding and infection. Although pruritus usually occurs in the skin, it can also occur in non-cutaneous sites, such as mucous membranes or the cornea. A variety of causes of pruritus are recognized, including external and exogenous effects, localized skin disorders, and systemic diseases. Wound healing after injury or surgery is often accompanied by localized itching. Pruritus can also be a component of inflammation.
Histamine is one of the most important mediators of itch, although other chemical substances have also been implicated, such as neuropeptides that act by releasing histamine from mast cells, and itching caused by them responds to antihistamines. Other substances act independently; therefore, antihistamines are not effective in some forms of pruritus.
A wide variety of treatment modalities for pruritus are reported, including nonspecific topical agents such as emollients and counter-irritants, topical drugs such as corticosteroids, agonists, such as cannabinoids or calcineurin inhibitors, local anesthetics, and antihistamines, anticonvulsants, antidepressants, and micro-opioid receptor antagonists, as well as by physical modalities, such as UV-based phototherapy, cooling, transcutaneous electrical nerve stimulation, and acupuncture. Some of these treatments are effective in pruritic conditions of a particular etiology, while others may show general but nonspecific benefit.
Other anti-pruritic and wound-healing agents reported for the treatment of skin disorders have involved the use of topically applied proteolytic enzyme compositions. In U.S. Pat. No. 3,003,917, compositions useful for the acceleration of wound healing include relaxin, a proteolytic enzyme or enzymes, and an amylolytic enzyme or enzymes. Relaxin is a protein hormone and is in the insulin family. The proteolytic enzymes which may be used in this formulation are trypsin, chymotrypsin, pepsin, papain, bromelain, ficin and mixtures of proteolytic enzymes obtained from bacteria. The amylolytic enzymes which may be used are mixtures of bacterial amylases, pancreatic or α-amylase and β-amylase. A particularly effective composition for accelerating wound healing comprises relaxin, trypsin, and pancreatic amylase, in respective weight ratios of 5:1:1.
In International Patent Publication Number WO 1984/002846, a topical ointment for skin surface wounds is described that includes wound-healing amounts papain, bromelain, trypsin, chymotrypsin, pancreatin, lipase, amylase, aloe extract and an organic astringent agent formulated in a carrier mixture of penetrating and non-penetrating emollient oils and a polyhydric alcohol emollient, with a plurality of protease. The ointment is reported to reduce inflammation at the site of skin-surface wounds and acts to enhance the normal anti-inflammatory activities of the body.
In International Patent Publication Number WO 2010/004367, the use of a mixture of superoxide dismutase and catalase enzymes for treating pruritus and alleviating its symptoms is reported.
In International Patent Number WO 8402846, a topical ointment for skin surface wounds comprising wound-healing amounts of papain, bromelain, trypsin, chymotrypsin, pancreatin, lipase, amylase, aloe extract and an organic astringent agent formulated in a carrier mixture of penetrating and non-penetrating emollient oils and a polyhydric alcohol emollient is reported. The ointment reportedly reduces inflammation at the site of skin-surface wounds and acts to enhance the normal anti-inflammatory activities of the body, particularly by enhancing the normal anti-inflammatory activity of proteolytic enzymes. The compositions utilized preferably include wound-cleansing amounts of topically-applied pancreatic digestive enzymes such as lipases and/or amylases, which are considered to affect the fats and carbohydrates contained in the structure of bacteria and viruses, wherein many types of viruses possess an outer cell envelope composed of protein, lipid and carbohydrate constituents. According to the WO'846 publication, amylase and/or lipase, in conjunction with the proteolytic enzymes, are thought to act synergistically to degrade the cell-envelope and protein and lipid components of the virus particle so as to inactivate the pathogenicity of viruses contained in or entering the wound. In this manner, wound-healing is purported to be aided by the control of infectious microorganisms.
In International Patent Publication Number WO 1999/046368, a method for treating wounds comprising the step of administering an effective amount of a carbohydrate-active enzyme is discussed that reportedly has broad-specificity for debriding burns and other wounds. According to the WO'368 publication, because of the high concentrations of glycosaminoglycans (GAGs) in skin, for burn patients, enzymes that degrade glycosaminoglycans are considered to be useful adjuncts to burn wound debridement. GAGs are sugar chains consisting of repeating polymers of acidic polysaccharides, composed of building blocks of the following sugars in various combinations: galactose, glucose, N-acetylglucosamine, N-acetylgalactosamine, glucuronic acid, galacturonic acid and iduronic acid. It is known that carbohydrates have important roles in the functioning of living organisms. In addition to their metabolic roles, carbohydrates are structural components of the human body, being covalently attached to numerous other entities such as proteins (i.e., as glycoproteins). Human skin is reported to contain 10% by weight of GAGs, which include heparin, heparan sulfate, chondroitin sulfate, hyaluronic acid (hyaluronan), dermatan sulfate, and keratan sulfate, with chondroitin sulfate being the most prevalent glycosaminoglycan. Chondroitin sulfate has β-1,3- and β-1,4-linkages between predominant monomeric units. In the WO'368 publication, the term “carbohydrate-active enzyme” is used to specifically encompass carbohydrate reducing enzymes, where examples of such enzymes include glycosaminoglycan reducing enzymes such as hyaluronidases, chondroitinases, dermatanases, heparanases, heparinases and keratanases, with preferred carbohydrate-active enzymes of chondroitinases and hyaluronidases.
In U.S. Patent Application 2013/0273026, a method for modulating inflammatory molecules with amylase, by modulating Immunoglobulin E (IgE) antibody mediated histamine release from an IgE receptor positive cell has been reported. The method is reportedly capable of releasing histamine in vitro or in vivo, wherein an effective dose of an amylase peptide or a derivative thereof is provided to the IgE receptor positive cell in vitro or in vivo under conditions that would permit binding of amylase to free IgE in solution to form an IgE-amylase binding pair, thereby inhibiting the binding of free IgE to the IgE receptor positive cell. IgE is described as a protein involved in the upregulation of a chronic inflammatory response (for example, the chronic inflammatory response observed in Type I diabetes). According to one embodiment disclosed in the '026 publication, disrupting the function of IgE with amylase provides an ameliorating effect on chronic inflammation. This process has purported efficacy relative to chronic inflammation in cystic fibrosis, Type I and Type II diabetes, such as by modulating serum insulin, treating obesity, stabilizing serum blood amylase for treating insulin resistance, modulating histamine levels in a mammal, and treating chronic inflammation. The compositions of the '026 publication are reported to be administered systemically, such as orally or by injection, topically, and transdermally.